The present invention relates to novel chromogenic crown ethers and to the use of the ethers as reagents for the selective extraction and colorimetric determination of lithium. The compounds of the invention have the structural formula: ##STR1## wherein X and Y are, respectively, (i) OH and NH.sup.+ ; (ii) O.sup.- and N, or (iii) O.sup.- and NH.sup.+. When X is OH and Y is NH.sup.+, the compound is systematically named, 1-(2-hydroxy-5-nitrobenzyl)-1-hydro-1-aza-4,7,10-trioxacyclododecane; when X is O.sup.- and Y is N, 1-(2-oxy-5-nitrobenzyl)-1-aza-4,7,10-trioxacyclodecane; and, when X is O.sup.- and Y is NH.sup.+, 1-(2-oxy-5-nitrobenzyl)-1-hydro-1-aza-4,7,10-trioxacyclododecane. All three of these compounds are, generically, chromogenic aza-12-crown-4 ethers.
Selective reagents which permit the isolation of a particular ion from a complex matrix or mixture of ions are of interest to those in the chemical or bio-chemical analytical fields. When the matrix in question includes two or more cations of the Group I metals, it is often difficult to selectively isolate one of the Group I cations from the mixture without interference from other cations in the system. With respect to biological systems, such as blood serum, which contains a relatively large amount of sodium ion, a reagent having the ability to selectively (and quantitatively) extract lithium ion in the presence of sodium ion is of interest for bio-chemical assays.
The ability of crown ethers to selectively extract alkali and alkaline earth metal ions has been recognized in the art [Pedersen, C. J., J.Am.Chem.Soc. 1967, 89, 7017]. Nonetheless, there has been little successful work in utilizing these compounds in analytical determinations until quite recently, e.g., U.S. Pat. No. 4,436,923 to Pacey and Bubnis, which describes a crown ether reagent which can be used for the spectrophotometric determination of potassium ion in the presence of sodium ion.
Of particular interest to the background of the present invention is the crown ether N-(2-hydroxy-5-nitrobenzyl)-aza-15-crown-5 ##STR2## which was reported to be a selective extractant for lithium ion. [Nakamura, H., Sakka, H., Takagi, M. and Ueno, K., Chem.Lett., 1981, 1305]. Although this compound exhibited good extraction efficiency for lithium ion (-log K.sub.LiL.sup.ex =9.15), the extraction efficiency of the reagent for sodium ion was of the same order of magnitude (-log K.sub.NaL.sup.ex =9.76). Thus the compound exhibited relatively poor selectivity in that it displayed only slightly more affinity for the lithium ion.
Another compound which is of interest to the chromogenic aza-12-crown-4 compounds of the present invention is the cryptand [2,1,1]. ##STR3## which was reported to extract lithium ions more selectively and more efficiently than the reagent of Nakamura et al. [Wu, Y. and Pacey, G., American Chemical Society 15th Central Regional Meeting, Miami University, Ohio, 1983, No. 18 (May 23-25, 1983)]. However, not only is the Wu et al cryptand difficult to synthesize, but the cryptand also requires an ion pairing agent, resazurin, in order to exhibit sensitivity to lithium. That is, the [2,1,1] cryptand itself is not sensitive to lithium ions.